次世代型有機酸塩基複合触媒の創製と高難度有機合成への応用

• Project/Area Number: 18H01975
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Tokyo University of Agriculture and Technology (2020-2021); Kyoto University (2018-2019)
• Principal Investigator: 加納 太一 東京農工大学, 工学(系)研究科(研究院), 教授 (40372560)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Granted (Fiscal Year 2021)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 有機触媒 / 酸触媒 / 塩基触媒 / アミン触媒 / 有機分子触媒 / 不斉合成 / アミン有機触媒 / 不斉触媒反応 / 酸塩基複合触媒 / 有機酸触媒 / 環化反応

Outline of Annual Research Achievements

本研究では、酸性の官能基と塩基性の官能基を併せ持つ、酸塩基複合触媒の開発を目指している。弱酸性の官能基と弱塩基性の官能基の双方を持った有機分子触媒は、アミノ酸であるプロリンに代表されるように数多く知られているが、強酸性の官能基や強塩基性の官能基が共存すると、酸塩基複合体を形成して不活性化するため、そうした官能基を酸塩基複合触媒に導入することは容易ではない。そこで剛直な母骨格にそれぞれの官能基を導入することで、分子内での酸塩基複合体形成を妨げる。また分子間の酸塩基複合体形成は、官能基周辺に立体障害を導入することで阻害できるかを検証する。本年度は、不斉素子として汎用されている軸不斉をもったビナフチルの代わりに、フェニルシクロプロパンを基本構造とする新しいアミン有機触媒による高難度の新規反応の開発に取り組んだ。この光学活性なアミン有機触媒は強酸性官能基を有した酸塩基複合触媒であり、ケチミンを求電子剤とした不斉マンニッヒ反応やα,β-不飽和ケチミンに対する不斉共役付加反応において、従来型の触媒より高い立体選択性、位置選択性で円滑に反応を進行させられることを見出した。本研究ではアルキル基とアルキニル基で置換された新しいケチミンの合成法を確立して、その有用性を示した。これらの反応において、ビナフチル骨格をもった従来型の触媒と選択性が異なる理由は、計算化学によって提案された遷移状態から明らかとなった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究ではビナフチルに代わる新しい不斉素子としてフェニルシクロプロパンが有効であることを見出している。それを基本構造に組み込んだアミン触媒に強酸性の官能基を導入すると、マンニッヒ反応や共役付加反応において従来型の触媒と比較して高い立体選択性で反応を進行させることに成功した。

Strategy for Future Research Activity

二重結合性をもったシクロプロパンが触媒の部分構造として有効であったことから、その知見を活かしてより簡便に合成可能な酸塩基複合触媒を設計して、研究の迅速化を図る。

Research Products

• [Int'l Joint Research] Lanzhou Institute of Chemical Physics(中国)
• [Journal Article] Practical Asymmetric Synthesis of Chiral Sulfoximines via Sulfur-Selective Alkylation (2022)
  • Author(s): Yoshiaki Maeda, Suguru Hamada, Yusuke Aota, Kazuya Otsubo, Taichi Kano, Keiji Maruoka
  • Journal Title: Journal of Organic Chemistry Volume: 87 Pages: 3652-3660
  • DOI: 10.1021/acs.joc.1c02424
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Phenylcyclopropane-based Chiral Amine Catalysts and Their Application in Asymmetric Reactions (2022)
  • Author(s): 本間千裕、加納太一
  • Journal Title: J. Syn. Org. Chem., Jpn. Volume: 80 Issue: 2 Pages: 92-102
  • DOI: 10.5059/yukigoseikyokaishi.80.92
  • NAID: 130008158523
  • ISSN: 0037-9980, 1883-6526
  • Peer Reviewed
• [Journal Article] Cu-Catalyzed O-alkylation of phenol derivatives with alkylsilyl peroxides (2021)
  • Author(s): Sakurai Shunya、Kano Taichi、Maruoka Keiji
  • Journal Title: Chem. Commun. Volume: 57 Pages: 81-84
  • DOI: 10.1039/d0cc07305a
  • Peer Reviewed
• [Journal Article] Construction of Chiral α-tert-Amine Scaffolds via Amine-catalyzed Asymmetric Mannich Reactions of Alkyl-substituted Ketimines (2021)
  • Author(s): Chihiro Homma, Aika Takeshima, Taichi Kano, Keiji Maruoka
  • Journal Title: Chemical Science Volume: 12 Pages: 1445-1450
  • DOI: 10.1039/d0sc05269h
  • Peer Reviewed
• [Journal Article] Asymmetric α-Hydroxylation of α-Aryl-δ-lactams with Molecular Oxygenunder Phase-Transfer Conditions (2021)
  • Author(s): Tomoaki Inukai, Taichi Kano, Keiji Maruoka
  • Journal Title: Organic Letters Volume: 23 Pages: 792-796
  • DOI: 10.1021/acs.orglett.0c04022
  • Peer Reviewed
• [Journal Article] Bifunctional Amino Sulfonamide-catalyzed Asymmetric Conjugate Addition to Alkenyl Alkynyl Ketimines as Enone Surrogates (2021)
  • Author(s): Chihiro Homma, Taichi Kano, Keiji Maruoka
  • Journal Title: Chemical Communications Volume: 57 Pages: 2808-2811
  • DOI: 10.1039/d0cc07842e
  • Peer Reviewed
• [Journal Article] Synthesis of Alkynyl Z-Ketimines and Their Application in Amine-catalyzed Asymmetric Mannich Reactions and Conjugate Addition (2021)
  • Author(s): Chihiro Homma, Masahiro Yamanaka, Taichi Kano, Keiji Maruoka
  • Journal Title: Tetrahedron Volume: 91 Pages: 132225-132225
  • DOI: 10.1016/j.tet.2021.132225
  • Peer Reviewed
• [Journal Article] Ni-Catalyzed C(sp2)－H Alkylation of N-Quinolylbenzamide Using Alkylsilyl Peroxides as Structurally Diverse Alkyl Sources (2021)
  • Author(s): Saori Tsuzuki, Shunya Sakurai, Akira Matsumoto, Taichi Kano, Keiji Maruoka
  • Journal Title: Chem. Commun. Volume: 57 Pages: 7942-7945
  • DOI: 10.1039/d1cc02983e
  • Peer Reviewed
• [Journal Article] Construction of a Quaternary Carbon Center by Catalytic Asymmetric Alkylation of 3-Arylpiperidin-2-ones under Phase-Transfer Conditions (2020)
  • Author(s): T. Inukai, T. Kano, and K. Maruoka
  • Journal Title: Angewandte Chemie International Edition Volume: 59 Pages: 2211-2214
  • DOI: 10.1002/anie.201913518
  • Peer Reviewed
• [Journal Article] Bronsted Acid-Catalyzed Intramolecular α-Arylation of Ketones with Phenolic Nucleophiles via Oxy-Allyl Cation Intermediates (2020)
  • Author(s): Aota Yusuke、Doko Yuki、Kano Taichi、Maruoka Keiji
  • Journal Title: European Journal of Organic Chemistry Volume: 2020 Pages: 1907-1911
  • DOI: 10.1002/ejoc.202000169
  • Peer Reviewed
• [Journal Article] Enantioselective Synthesis of Monosaccharide Analogues by Two-Step Sequential Enamine Catalysis: Benzoyloxylation and Aldol Reaction (2020)
  • Author(s): Shimogaki Mio、Takeshima Aika、Kano Taichi、Maruoka Keiji
  • Journal Title: European Journal of Organic Chemistry Volume: - Pages: 2028-2032
  • DOI: 10.1002/ejoc.202000073
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of Ketone-Based Brominating Agents (KBA) for the Practical Asymmetric α-Bromination of Aldehydes Catalyzed by Tritylpyrrolidine (2020)
  • Author(s): Takeshima Aika、Shimogaki Mio、Kano Taichi、Maruoka Keiji
  • Journal Title: ACS Catalysis Volume: - Pages: 5959-5963
  • DOI: 10.1021/acscatal.0c01596
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Organocatalytic Formal (3 + 2) Cycloaddition toward Chiral Pyrrolo[1,2-a]indoles via Dynamic Kinetic Resolution of Allene Intermediates (2020)
  • Author(s): Jian-Fei Bai, Lulu Zhao, Fang Wang, Fachao Yan, Taichi Kano, Keiji Maruoka, Yuehui Li
  • Journal Title: Organic Letters Volume: 22 Pages: 5439-5445
  • DOI: 10.1021/acs.orglett.0c01812
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Synthesis of Electron-Deficient Chiral Biphenols and Their Applications in Catalytic Asymmetric Reactions (2020)
  • Author(s): Kento Yasumoto, Taichi Kano, Keiji Maruoka
  • Journal Title: Journal of Organic Chemistry Volume: 85 Pages: 10232-10239
  • DOI: 10.1021/acs.joc.0c01116
  • Peer Reviewed
• [Journal Article] Cu-Catalyzed Enantioselective Alkylarylation of Vinylarenes Enabled by Chiral Binaphthyl?BOX Hybrid Ligands (2020)
  • Author(s): Sakurai Shunya、Matsumoto Akira、Kano Taichi、Maruoka Keiji
  • Journal Title: J. Am. Chem. Soc. Volume: 142 Pages: 19017-19022
  • DOI: 10.1021/jacs.0c09008
  • Peer Reviewed
• [Journal Article] CuCl2‐Mediated Oxidative Intramolecular α‐Arylation of Ketones with Phenolic Nucleophiles via Oxy‐Allyl Cation Intermediates (2020)
  • Author(s): T. Mochimatsu, Y. Aota, T. Kano, and K. Maruoka
  • Journal Title: Chemistry Asian Journal Volume: 15 Pages: 3816-3819
  • DOI: 10.1002/asia.202001032
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of Chiral Sulfoximines via the S-Arylation of Sulfinamides (2019)
  • Author(s): Y. Aota, T. Kano, and K. Maruoka
  • Journal Title: Journal of the American Chemical Society Volume: 141 Pages: 19263-19268
  • DOI: 10.1021/jacs.9b11298
  • Peer Reviewed
• [Journal Article] Efficient Synthesis of Cyclic Sulfoximines from N-Propargylsulfinamides through Sulfur-Carbon Bond Formation (2019)
  • Author(s): Y. Aota, Y. Maeda, T. Kano, and K. Maruoka
  • Journal Title: Chemistry-A European Jornal Volume: 25 Pages: 15755-15758
  • DOI: 10.1002/chem.201904501
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of Chiral Sulfoximines through the S-Alkylation of Sulfinamides (2019)
  • Author(s): Y. Aota, T. Kano, and K. Maruoka
  • Journal Title: Angewandte Chemie International Edition Volume: 58 Pages: 17661-17665
  • DOI: 10.1002/anie.201911021
  • Peer Reviewed
• [Journal Article] Synthesis of Phenylcyclopropane-Based Secondary Amine Catalysts and Their Applications in Enamine Catalysis (2019)
  • Author(s): A. Takeshima, T. Kano, and K. Maruoka
  • Journal Title: Organic Letters Volume: 21 Pages: 8071-8074
  • DOI: 10.1021/acs.orglett.9b03070
  • NAID: 120006731151
  • Peer Reviewed
• [Journal Article] Asymmetric Synthesis of Chiral 1,4-Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines (2019)
  • Author(s): J.-F. Bai, K. Yasumoto, T. Kano, and K. Maruoka
  • Journal Title: Angewandte Chemie International Edition Volume: 58 Pages: 8898-8901
  • DOI: 10.1002/anie.201904520
  • Peer Reviewed
• [Journal Article] One-Pot Synthesis of Less Accessible N-Boc-Propargylic Amines Through BF3-Catalyzed Alkynylation and Allylation Using Boronic Esters (2019)
  • Author(s): K. Yasumoto, T. Kano, and K. Maruoka
  • Journal Title: Organic Letters Volume: 21 Pages: 3214-3217
  • DOI: 10.1021/acs.orglett.9b00931
  • Peer Reviewed
• [Journal Article] Synthesis of 1-Aminoindenes through Aza-Prins-Type Cyclization (2018)
  • Author(s): J.-F. Bai, K. Yasumoto, T. Kano, and K. Maruoka
  • Journal Title: Chemistry-A European Journal Volume: 24 Pages: 10320-10323
  • DOI: 10.1002/chem.201802448
  • Peer Reviewed
• [Journal Article] BF3-Catalyzed Synthesis of Cyclic Carbamates from Boc-Protected Aminals and Alkynes (2018)
  • Author(s): T. Kano, K. Yasumoto, and K. Maruoka
  • Journal Title: Asian Journal of Organic Chemistry Volume: 7 Pages: 1575-157
  • DOI: 10.1002/ajoc.201800289
  • Peer Reviewed
• [Presentation] アミン触媒による三連続不斉中心の構築 (2022)
  • Author(s): 加納太一
  • Organizer: 新学術領域「ハイブリッド触媒」第5回公開シンポジウム
• [Presentation] アミン触媒によるアルキニル置換Z-ケチミンの不斉マンニッヒ反応および不斉共役付加反応の開発 (2021)
  • Author(s): 本間千裕、加納太一、丸岡啓二
  • Organizer: 第101春季年会
• [Presentation] 新規臭素化剤の開発とアミン触媒によるアルデヒドのα-不斉臭素化反応への応用 (2020)
  • Author(s): 武島愛夏、下垣実央、加納太一、丸岡啓二
  • Organizer: 第49回 複素環化学討論会
• [Presentation] キラル相間移動触媒を用いたラクタムの不斉アルキル化による不斉四級炭素の構築 (2019)
  • Author(s): 犬飼 倫聡・加納 太一・丸岡 啓二
  • Organizer: 日本化学会春季年会
• [Presentation] 新規光学活性アミノスルホンアミド触媒の開発と応用 (2019)
  • Author(s): 武島 愛夏・加納 太一・丸岡 啓二
  • Organizer: 日本化学会春季年会
• [Presentation] Enantioselective Mannich Reaction of Z-Ketimines using a Secondary Amine Catalyst (2019)
  • Author(s): HOMMA, Chihiro; MARUYAMA, Hiroki; KANO, Taichi; MARUOKA, Keiji
  • Organizer: 日本化学会春季年会
• [Presentation] Lewis acid-catalyzed Petasis-type reaction between in-situ generated N-Boc-protected imines and alkynyl boronate esters (2019)
  • Author(s): YASUMOTO, Kento; KANO, Taichi; MARUOKA, Keiji
  • Organizer: 日本化学会春季年会
• [Presentation] 硫黄-炭素結合形成による環状スルホキシイミンの合成 (2019)
  • Author(s): 前田 祥明・青田 雄介・加納 太一・丸岡 啓二
  • Organizer: 日本化学会春季年会
• [Presentation] スルフィンアミドの硫黄選択的アルキル化によるスルホキシイミンの不斉合成法の開発 (2019)
  • Author(s): 青田 雄介・加納 太一・丸岡 啓二
  • Organizer: 日本化学会春季年会